1,2-Dichloroethane → 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(3-methoxy-4-methylphenyl)acetamido)benzamido) methyl)phenyl 4-(heptyloxy)benzoate

HRID 923535Notes

Reaction equation

HRID 923535 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:10][C:11]([OH:13])=O)[CH:6]=[CH:7][C:8]=1[CH3:9].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[CH2:28]([O:35][C:36]1[CH:69]=[CH:68][C:39]([C:40]([O:42][C:43]2[CH:48]=[CH:47][C:46]([CH2:49][N:50]([CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C:51](=[O:59])[C:52]3[CH:57]=[CH:56][C:55]([NH2:58])=[CH:54][CH:53]=3)=[CH:45][CH:44]=2)=[O:41])=[CH:38][CH:37]=1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>CN(C=O)C>[CH2:28]([O:35][C:36]1[CH:69]=[CH:68][C:39]([C:40]([O:42][C:43]2[CH:48]=[CH:47][C:46]([CH2:49][N:50]([CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C:51](=[O:59])[C:52]3[CH:53]=[CH:54][C:55]([NH:58][C:11](=[O:13])[CH2:10][C:5]4[CH:6]=[CH:7][C:8]([CH3:9])=[C:3]([O:2][CH3:1])[CH:4]=4)=[CH:56][CH:57]=3)=[CH:45][CH:44]=2)=[O:41])=[CH:38][CH:37]=1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 91183902-(3-Methoxy-4-methylphenyl)acetic acidHCID 892531254-((4-amino-N-(2-(tert-butoxy)-2-oxoethyl)benzamido)methyl)phenyl 4-(heptyloxy)benzoate

Product 1

HCID 892530204-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(3-methoxy-4-methylphenyl)acetamido)benzamido) methyl)phenyl 4-(heptyloxy)benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Prepared using General Procedures 6 and 8: To 2-(3-methoxy-4-methylphenyl)acetic acid (14.1 mg, 0.08 mmol) were added HOBT (12.0 mg, 0.08 mmol) in DMF (0.1 mL) and EDC (15.0 mg, 0.08 mmol) in DMF (0.1 mL). After stirring at room temperature for 30 min, 4-((4-amino-N-(2-(tert-butoxy)-2-oxoethyl)benzamido)methyl)phenyl 4-(heptyloxy)benzoate INT-4 (30 mg, 0.05 mmol) and TEA (0.019 mL, 0.10 mmol) in DMF (0.3 mL) were added. The reaction was stirred for 18 h then purified by preparative HPLC to provide 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(3-methoxy-4-methylphenyl)acetamido)benzamido)methyl)phenyl 4-(heptyloxy)benzoate. To 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(3-methoxy-4-methylphenyl)acetamido)benzamido)methyl)phenyl 4-(heptyloxy)benzoate in DCM (1.0 mL) was added TFA (0.2 mL). The reaction was stirred at 30° C. for 6 h. The reaction was concentrated to afford 22.3 mg (65%) of 2-(N-(4-((4-(heptyloxy)benzoyl)oxy)benzyl)-4-(2-(3-methoxy-4-methylphenyl)acetamido)benzamido)acetic acid 4. LCMS-ESI (m/z) calculated for C40H44N2O8: 680; no m/z observed, tR=11.45 min (Method 2). 1H NMR (400 MHz, DMSO) δ 10.32 (s, 1H), 8.06 (d, J=8.8 Hz, 2H), 7.64 (d, J=8.4 Hz, 2H), 7.43 (d, J=7.2 Hz, 1H), 7.40-7.28 (m, 3H), 7.24 (d, J=8.5 Hz, 2H), 7.17-7.02 (m, 3H), 6.91 (s, 1H), 6.79 (d, J=7.5 Hz, 1H), 4.62 (d, J=36.2 Hz, 2H), 4.08 (t, J=6.5 Hz, 2H), 3.95 (d, J=28.6 Hz, 2H), 3.77 (s, 3H), 3.60 (s, 2H), 2.10 (s, 3H), 1.74 (dd, J=9.8, 4.8 Hz, 2H), 1.48-1.24 (m, 8H), 0.86 (d, J=7.0 Hz, 3H).

Workup

  1. customPrepared
  2. stirringThe reaction was stirred for 18 h
  3. customthen purified by preparative HPLC

Sources & evidence

ORD record
ord-4da826d2ca5d45c786a11c1d155b0848
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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